Core B: Clinical Core Project Summary/Abstract The Clinical Core is critical to achieving the ultimate goal of the UCI ADRC, which is to identify means to prevent, mitigate, and eradicate Alzheimer's disease (AD), by translating basic research findings into clinical advances. As such, the objective of the Clinical Core is to recruit and longitudinally characterize human participants who span the spectrum of normal human aging, preclinical AD, mild cognitive impairment, and dementia. This will include collection of neurological, neuropsychological, novel biomarker, and stem cell data. Recognizing the heterogeneity of AD and the importance of studying AD across the lifespan, the Clinical Core follows 3 cohorts: (1) The longitudinal cohort which is central to all ADCs has a fundamental role in the characterization of healthy older adults as well as participants in pre-clinical, early stage, and AD dementia. (2) A special cohort of adults with Down syndrome represents the largest group of individuals with early-onset AD, and provides insights into preclinical AD pathogenesis. (3) A special cohort of the oldest old provides data on successful aging, yet remain at high risk of developing AD and other dementias, and represent the fastest- growing segment of the U.S. population. The Clinical Core will provide well-characterized participants, their data and biospecimens, and ultimately brain tissue for the Data Core for sharing with NACC, for the IPS Cell Core for generation and study of IPS cells, for the Neuropathology Core for genetic, biomarker, and neuropathological study and submission to NCRAD, and for the Projects which will include MRI imaging studies, neuropathological studies, and use of IPS cells. In addition, the Clinical Core will provide participants for multi-center imaging initiatives and multi-center AD prevention and clinical trials, including ADCS trials. Recognizing the long preclinical course of AD and the importance of individuals with preclinical AD for epidemiologic, prevention, and treatment research, the Clinical Core will establish a registry of individuals with normal cognition but at high risk of developing AD due to advanced age or presence of amyloid biomarker. The Clinical Core will interact with the ORE Core to increase underserved minority participation in AD clinical research, including individuals with Down syndrome and Chinese-Americans. Finally, the Clinical Core will provide a rich training environment to educate the next generation of AD researchers and clinicians.